T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease.
T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease.
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DOI：
10.3389/fimmu.2022.1016038
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
非结核分枝杆菌（NTM）疾病易感性的免疫学机制知之甚少。为了了解NTM的发病机制，我们评估了先天性和抗原特异性的适应性免疫反应，以鸟分枝杆菌复合体（MAC）在无症状的个人与以前的历史MAC肺病（MACDZ）。我们假设Mav特异性免疫应答与MAC肺病的易感性相关。我们测量MAC，NTM，或MAC/Mtb特异性T细胞反应的细胞因子的产生，表面标志物的表达，并在27个MACDZ个人和32个健康对照的全球基因表达的分析。我们还分析了17例MACDZ和17例健康对照者的鸟分枝杆菌感染和未感染外周血单核细胞的整体基因表达。与对照组相比，我们无法检测到MACDZ中对MAC特异性试剂的T细胞应答增加，而对非分枝杆菌衍生抗原的应答得以保留。MACDZ个体具有较低的Th 1和Th 1 * T细胞群频率。此外，MACDZ受试者在用分枝杆菌肽库（MTB 300）刺激的PBMC中具有较低的转录应答。相比之下，整体基因表达分析表明，在未感染和M。与对照相比，来自MACDZ受试者的禽流感感染的单核细胞，即体外高度炎症反应。总之，这些数据表明一种新的免疫缺陷，它是MAC发病机制的基础，包括在治疗完成后持续数年的先天性和适应性失调。
Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment.
DOI：
10.1016/j.jctube.2020.100189
发表时间：
2020-12
影响因子：
2
作者：
Tam WO;Wong CF;Wong SSY;Kwan CLY
通讯作者：
Kwan CLY
影响因子：
3.7
作者：
Checkley AM;Wyllie DH;Scriba TJ;Golubchik T;Hill AV;Hanekom WA;McShane H
通讯作者：
McShane H